Sustainable development has clearly taken on a global dimension, even if in recent years it has increasingly been acknowledged that there is a close mutual interaction between local and global processes. Politicians, economists and practitioners have realised that regional differences and particularities have become very important for building a people-based development which is not only goods-based. Thus, some new keywords for endogenous self-sustainable development are: networks, knowledge and local milieux. The integration of sustainable development aspects in spatial planning, territory governance and development has become stronger and stronger, combined with a spread of local knowledge and the preservation of both the cultural and environmental heritage. This paper considers all these factors and tries to explain these types of relationships, starting from the idea of city network as a basis for global competition, and moving on towards discussing the role of universities and scientific parks as institutions for knowledge production and dissemination. Finally, the important role of cultural heritage in a territory is investigated, as tool for building a culture-based growth that should increase social cohesion, local identity and equity. Although largely descriptive, this analysis is of special use to those teaching courses in the fields of architecture, planning and civil engineering, where a broader knowledge of city networks offers a more solid basis upon which awareness of sustainability may be built.